Studies will be carried out on human subjects to elucidate the nature of the bile acid metabolism defect in patients with cholesterol gallstones. Specifically we will continue our investigations on the liver cholesterol precursor sites of bile acid, biliary cholesterol and plasma cholesterol utilizing the "T" tube patient model administered various precursors (such as H3 mevalonate and C14 cholesterol). Other investigations are planned on the effect of bile acids on the synthesis and regulation of primary bile acid by the liver of man. These experiments will be concerned with how cholic, chenodeoxycholic, and deoxycholic acid affect the synthesis of their own and other bile acids and what specific enzyme sites are definitively rate limiting. Preliminary experiments have shown that the 7 alpha-hydroxylase system is rapidly and markedly depressed by the administration of chenodeoxycholic acid. This leads to a marked depression of both cholic and chenodeoxycholic acid synthesis.